The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis

Evertine Wesselink; Michiel Balvers; Martijn J L Bours; Johannes H W de Wilt; Renger F Witkamp; Harm van Baar; Anne J M R Geijsen; Henk van Halteren; Eric T P Keulen; Dieuwertje E Kok; Ewout A Kouwenhoven; Jody van den Ouweland; Moniek van Zutphen; Matty P Weijenberg; Ellen Kampman; Fränzel J B van Duijnhoven

doi:10.1177/1756284820923922

The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis

Therap Adv Gastroenterol. 2020 May 27:13:1756284820923922. doi: 10.1177/1756284820923922. eCollection 2020.

Authors

Evertine Wesselink¹, Michiel Balvers², Martijn J L Bours³, Johannes H W de Wilt⁴, Renger F Witkamp², Harm van Baar², Anne J M R Geijsen², Henk van Halteren⁵, Eric T P Keulen⁶, Dieuwertje E Kok², Ewout A Kouwenhoven⁷, Jody van den Ouweland⁸, Moniek van Zutphen², Matty P Weijenberg³, Ellen Kampman², Fränzel J B van Duijnhoven²

Affiliations

¹ Division of Human Nutrition and Health, Wageningen University & Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands.
² Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
³ Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
⁴ Department of Surgery, Radboud University Medical Centre, Nijmegen, The Netherlands.
⁵ Department of Internal Medicine, Admiraal de Ruyter Ziekenhuis, Goes, The Netherlands.
⁶ Department of Gastroenterology, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands.
⁷ Department of Surgery, Hospital Group Twente ZGT, Almelo, The Netherlands.
⁸ Department of Clinical Chemistry, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.

Abstract

Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D₃ (25(OH)D₃) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis.

Methods: Circulating 25(OH)D₃ levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D₃ levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D₃ and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted.

Results: Higher 25(OH)D₃ levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β -0.06, 95% CI -0.08 to -0.04). In addition, 25(OH)D₃ levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β -0.17, 95% CI -0.25 to -0.08). In addition, a significant inverse association between 25(OH)D₃ levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D₃ and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D₃ and IL8 and hsCRP levels were observed.

Conclusions: Serum 25(OH)D₃ levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D₃-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.

Keywords: 25(OH)D3; colorectal cancer; cytokines; inflammatory markers; interleukin 6.